Early weaning causes undernutrition for a short period and programmes some metabolic syndrome components and leptin resistance in adult rat offspring

Abstract

Maternal malnutrition during lactation programmes for overweight and central leptin resistance in adulthood. The inhibition of lactation by maternal treatment with bromocriptine (a prolactin inhibitor) programmes for obesity, hyperleptinaemia and leptin resistance. Here, we evaluated the short-and long-term effects of early weaning (EW) on body-weight regulation, leptin signalling, and hormone and lipid profiles in rats offspring. Lactating rats were separated into two groups: EW -dams were wrapped with a bandage to interrupt the lactation in the last 3 d of lactation; control -dams whose pups had free access to milk during all lactation (21 d). Data were significant at P, 0·05. At weaning, EW pups presented lower body weight (210 %), length (24 %), visceral fat (2 40 %), total fat (2 30 %), serum leptin (273 %), glycaemia (210 %), serum insulin (220 %) and insulin resistance index (IRI; 2 30 %), but higher total body protein content (þ 40 %). At 180 d, EW offspring showed hyperphagia, higher length (þ 3 %), body weight (þ8 %), visceral and total fat (þ36 and 84 %), serum TAG (þ 96 %), glycaemia (þ15 %), leptinaemia (þ185 %) and IRI (þ 29 %); however, they showed lower total protein content (223 %), leptin:body fat ratio (41 %), prolactinaemia (2 38 %) and adiponectinaemia (259 %). Despite unchanged leptin receptor (OB-R) and signal transducer and activator of transcription 3 (STAT3), they displayed lower hypothalamic janus tyrosine kinase 2, phosphorylated STAT3 and a higher suppressor of cytokine signalling 3 levels, suggesting a central leptin resistance. Adult rats that were early weaned displayed higher adiposity, insulin resistance and dyslipidaemia, which are related to metabolic syndrome development. Our model reinforces the idea that neonatal malnutrition caused by shortening of the lactation period is important for metabolic programming of future diseases.

Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition

“…Early weaning changes serum leptin levels in weaned animals (Bonomo et al 2005, Lima et al 2011. This early change in the leptin level is critical for establishing neural circuitry in the hypothalamus (Bouret et al 2004) at a different set point of regulation.…”

“…This method programs for obesity, hyperleptinemia, leptin resistance (Bonomo et al 2007), and hypothyroidism (Bonomo et al 2008), and symptoms (including insulin resistance and an altered lipid profile) are similar to those of metabolic syndrome (Moura et al 2009). More recently, we obtained a similar profile in adult animals with a non-pharmacological model where a maternal bandage was used to cover the teats of the dam in the late lactation, thus also inducing an early weaning of offspring (Lima et al 2011(Lima et al , 2013.…”

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…The insulin resistance index (IRI) was calculated by the product of fasting insulin (µIU/mL) × fasting glucose (mmol/L) (Fagundes et al 2009, Lima Nda et al 2011, Li et al 2012.…”

Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood

“…These pups, despite the lower body adiposity, had hyperleptinemia, most likely caused by transfer of leptin via milk (Bonomo et al, 2005). In a later study, our laboratory developed another early-weaning model (without the use of BRO) in which the dams were wrapped with a bandage during the last 3 days of lactation (Lima et al, 2011). As a result, the pups had no access to milk and, at weaning, were undernourished and hypoleptinemic, just the opposite of what was observed with the pharmacological early-weaning model.…”